title: Overexpressed let-7a inhibits glioma cell malignancy by directly targeting K-ras, independently of PTEN.
abstract: BACKGROUND
  Altered expression of micro(mi)RNAs has been shown to be associated with tumorigenesis and tumor progression. The expression of phosphatase and tensin homolog (PTEN) plays an important role in glioma and is regarded as a prognostic marker of glioma patients. The goal of this study was to investigate the function of lethal (let)-7a miRNA in glioma cell lines with different PTEN phenotypes.
  
  
  METHODS
  One hundred ninety-eight glioma tissues were used to profile miRNA expression.
  
  
  RESULTS
  Let-7a was shown to have lower expression in high-grade glioma than in low-grade glioma. Low expression of let-7a was correlated with poor prognosis of primary glioblastoma patients. We demonstrated that K-ras was a functional target for let-7a to induce cell cycle arrest, apoptosis, and inhibition of cell migration and invasion in vitro. Our further results showed no difference in malignancy inhibition induced by let-7a in 4 glioma cells, including U87 (PTEN null), U251 (PTEN mutant), LN229 (PTEN wild type), and LN229 (PTEN small interfering RNA). The phosphatidylinositol-3 kinase/Akt and mitogen-activated protein kinase/extracellular signal-regulated kinase pathways were inhibited by let-7a, and the inhibition effects had no difference in 4 glioma cells. We demonstrated that let-7a could induce suppression of glioma in vivo by generating a glioma xenograft model.
  
  
  CONCLUSIONS
  Our results indicated that let-7a suppresses its target transcript K-ras and inhibits glioma malignancy independent of PTEN expression.
authors.affiliation: Corresponding Authors: Yong-Ping You, PhD, Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. YYPL9@njmu.edu.cn); Ning Liu, PhD, Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 China (liuning0853@126.com.
authors.forename: Xi-Rui
authors.initials: XR
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Luo
authors.forename: Hai-Lin
authors.initials: HL
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.forename: Xie-Feng
authors.initials: XF
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.forename: Ying-Yi
authors.initials: YY
authors.lastname: Wang
authors.forename: Jun-Xia
authors.initials: JX
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Chun-Sheng
authors.initials: CS
authors.lastname: Kang
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: You
mesh_terms: D000818:Animals; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C117307:KRAS protein, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C487931:mirnlet7 microRNA, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: K-ras; PTEN; glioma; let-7a; miRNA